Investigação de perda de heterozigosidade e expressão da proteína Ki-67 em lesão liquenóide oral associada ao amálgama

Abstract

The Amalgam-associated oral lichenoid lesion (AAOLL) is an infrequent disease of uncertain pathogenesis. The lesion shows clinical and histopathological features similar to oral lichen planus (OLP), which is considered a lesion with malignant transformation potential. Molecular researches in order to improve knowledge of the pathogenesis and clinical behavior of AAOLL are still scarce. The purpose of the current study was to evaluate the loss of heterozygosity - LOH in AAOLL, in OLP, and in normal oral mucosa (NOM) using polymorphic microsatellite markers at chromosome regions 9p22, 11q13.4 and 17p13.1, located around important tumor suppressor genes and to evaluate the immunohistochemical expression of Ki-67 protein in the same samples. The sample comprised 09 AAOLLs, 10 OLPs and 8 NOMs matched by patients gender and age. The LOH at chromosome regions 9p22, 11q13.4 and 17p13.1 was evaluated by microsatellite polymorphic markers D9S157, D9S162, D9S171, D11S1369, TP53, AFM238WF2. Cell proliferation was assessed by immunohistochemical expression of Ki-67 (MIB-1) in eight AAOLL, ten OLP and eight NOM. AAOLL exhibited LOH at 3 of 6 LOH markers (AFM238WF2, D9S157 AND D11S1369), while OLP demonstrated LOH at two of these markers (AFM238WF2, D9S157) while NOM showed no LOH. The allelic loss were most frequently in marker AFM238WF2 (17p13.1, 21%) and D9S157 (9p22, 17,64%). The mean fractional allelic loss of AAOLL was 26,6% whereas mean fractional allelic loss of OLP was 7,5%. Immunohistochemistry revealed nuclear positivity ranging from 0,29% to 28% of the cells and there was no association between cell proliferation and LOH in LLOAA e LPB (p>0,05). Our study shows that AAOLL, similar to OLP, exhibits LOH, irrespective of cell proliferation index. Despite the lack of association between LOH and cell proliferation we can assume that LOH occurs in AAOLL and it should be considered in the pathogenesis of this lesion.